Pediatric patients that received a transplanted kidney will receive immunosuppressive medication-the calcineurin inhibitor (tacrolimus) and antiproliferative agent (MMF)-until they will be randomized between week 4 and 6 to receive either the same treatment or to switch to the investigational drug everolimus. The patients will be followed up until 3 years after transplantation to evaluate the efficacy, tolerability and safety of the treatments and to assess their impact on renal function.

• Register: EUCTR
• Last refreshed on: 15 October 2018
• Main ID: EUCTR2010-024381-21-HU
• Date of registration: 08/07/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Pediatric patients that received a transplanted kidney will receive immunosuppressive medication-the calcineurin inhibitor (tacrolimus) and antiproliferative agent (MMF)-until they will be randomized between week 4 and 6 to receive either the same treatment or to switch to the investigational drug everolimus. The patients will be followed up until 3 years after transplantation to evaluate the efficacy, tolerability and safety of the treatments and to assess their impact on renal function.
• Scientific title: A 12-month, multicenter, open label, randomized, controlled study to evaluate the efficacy, tolerability and safety of early introduction of everolimus, reduced CNI, and early steroid elimination compared to standard CNI, mycophenolate mofetil and steroid regimen in paediatric renal transplant recipients with a 24-month additional safety follow-up - not applicable
• Date of first enrolment: 29/07/2011
• Target sample size: 106
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024381-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, France, Germany, Hungary, Italy, Norway, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Public Information Desk
• Affiliation: Novartis Hungary Kft. Pharma

• Name: Public Information Desk
• Affiliation: Novartis Hungary Kft. Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria at baseline (transplantation)
1-Written informed consent/assent must be obtained from the parent(s) or legal guardian before any assessment is performed.
2- Primary paediatric kidney transplant greater than or equal to 1 year and younger than 18 years receiving a primary deceased donor or non-HLA identical living donor (related or unrelated) renal transplant.

Inclusion criteria at randomization (4-6 weeks after transplantation)
1-Patients on TAC + MMF + steroids.
2- Renal function with eGFR > 50 ml/min/1.73 m2.
Are the trial subjects under 18? yes
Number of subjects for this age range: 106
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
exclusion criteria at baseline:
1- Recipients of kidneys from donors with known renal disease (such as diabetes nephropathy, nephrosclerosis), at the time of transplant.
2 - Recipients of a kidney with a cold ischemia time > 24 hours.
3 - Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
4 - History of hypersensitivity or contraindications to any of the study drugs or to drugs of similar chemical classes, or to any of the excipients.
5 - History of malignancy of any organ system treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

other protocol-defined exclusion criteria may apply

Exclusion criteria at Randomization (4-6 weeks after transplantation)
1 - Patients with ongoing or currently treated episodes of acute rejection (any grade) or a steroid resistant acute rejection at the time of randomization.
2 - Patients who experienced acute cellular rejection (Banff =1B) or any antibody mediated acute rejection at any time before randomization.
3 - Patients with ongoing wound healing problems, clinically significant wound infection requiring continued therapy or other severe surgical complication in the opinion of the investigator.
4 - Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and can not discontinue the treatment (see Appendix 6 for list of medications).
5 - Patients with nephrotic range proteinuria (protein to creatinine ratio =2.0 mg/mg or 200 mg/mmol.

other protocol-defined exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Prevention of acute rejection in paediatric recipients of a renal transplant
MedDRA version: 19.0 Level: SOC Classification code 10038359 Term: Renal and urinary disorders System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: Certican
Product Name: Certican 0,25 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Trade Name: Certican
Product Name: Certican 0,5 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Certican
Product Name: Certican 0,75 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-

Trade Name: Certican
Product Name: Certican 1 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Certican
Product Name: Certican 0,1 mg
Product Code: RAD001
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.1-

Trade Name: Certican
Product Name: Certican 0,25 mg
Product Code: RAD001
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Trade Name: Prograf
Product Name: Prograf 0,5 mg
Product Code: FK-506
Pharmaceutical Form: Capsule, hard
INN or P

Primary Outcome(s)

Secondary Objective: - To evaluate each of the components of the composite efficacy endpoint
- To evaluate the time to event and severity of BPAR
- To evaluate incidence of biopsy proven antibody mediated rejection
- Incidence/progression of chronic allograft nephropathy (Interstitial Fibrosis and Tubular Atrophy IF/TA) by histopathology.
- Assessment of growth and development, including linear growth, sexual maturation, hormonal gonadal axis (estradiol, testosterone, LH, FSH, inhibin B), TSH, T3 and T4

Main Objective: - To estimate the rate of the composite efficacy endpoint of BPAR, graft loss or death at 12 months post transplantation in primary paediatric kidney transplant recipients converted at 4-6 weeks post-transplantation from MMF + standard TAC regimen and steroids, to everolimus + reduced dose TAC regimen and steroid withdrawal at 6 months, versus continuation of MMF + standard TAC regimen and steroids.
- To evaluate renal function assessed by Glomerular Filtration Rate (eGFR) estimated by the Schwartz formula (abbreviated and extended) at month 12.

Timepoint(s) of evaluation of this end point: Month 12 after transplantation.

Primary end point(s): 1- The incidence of composite efficacy failure including BPAR, death, and graft loss at 12 months. Local biopsy readings will be used to determine the occurrence of BPAR.
2- Renal function will be assessed by eGFR estimated by the Schwartz formula (abbreviated and extended) at month 12.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Month 12 and 36 after transplantation.

Secondary end point(s): 1- Components of the composite efficacy endpoint;
2- Incidences of biopsy proven antibody mediated rejection
3- Incidence/progression of chronic allograft nephropathy (interstitial fibrosis and tubular atrophy, IF/TA);
4- Safety (evolution of renal function over time, incidence of proteinuria, the frequency of drug-related side effects (CNI-related, mTOR-inhibitor-specific or MMF-class effects), assessment of growth and development, the frequency of AEs/Infections, SAEs.

Secondary ID(s)

CRAD001A2314

Source(s) of Monetary Support

Novartis Pharma Services AG